MIT Researchers Engineer Programmable Gut Bacteria
MIT researchers have developed sensors, memory switches, and circuits that can be encoded in common human gut bacteria. These basic computing elements will allow the bacteria to sense, memorize, and respond to signals in the gut. Future medical applications of programmable gut bacteria might include early detection and treatment of diseases.
In a Cell Systems paper titled “Programming a Human Commensal Bacterium, Bacteroides thetaiotaomicron, to Sense and Respond to Stimuli in the Murine Gut Microbiota,” the researchers described a series of computing elements, sensors, memory switches, and circuits that can be encoded in common human gut bacteria. The paper, which is freely available online at the moment, states that “These results provide a blueprint for engineering new chassis and a resource to engineer Bacteroides for surveillance of or therapeutic delivery to the gut microbiome.”
Advanced Genetic Computing Circuits for Noninvasive Diagnostics and Therapeutics
Genetic circuits had previously been built inside model organisms such as E. coli, but this time the researchers wanted to work with common bacteria abundantly present in human guts. “We wanted to work with strains like B. thetaiotaomicron that are present in many people in abundant levels, and can stably colonize the gut for long periods of time,” said team co-leader Timothy Lu.
The team developed a series of genetic parts that can be used to precisely program gene expression within the bacteria. “Using these parts, we built four sensors that can be encoded in the bacterium’s DNA that respond to a signal to switch genes on and off inside B. thetaiotaomicron,” said team co-leader Christopher Voigt.
The researchers added to the bacteria a form of genetic memory to enable them to sense, remember and report on pathologies in the gut, including signs of bleeding or inflammation. To do this they used proteins that can record information into bacterial DNA by acting on specific DNA addresses. The scientists also implemented a technology known as CRISPR interference, which can be used to control which genes are turned on or off in a bacterium.
“We aim to expand our genetic toolkit to a wide range of bacteria that are important commensal organisms in the human gut,” said Lu, adding that programmable bacteria that sense and respond to signs of disease could also be used elsewhere in the body and include more advanced genetic computing circuits for noninvasive diagnostics and therapeutics.
The progmammable bacteria have been tested in mice. Though it will take time to refine, test and deploy programmable bacteria in human, we can envisage the possibility of engineered cells, permanently resident in our guts, which keep us healthy. Tom Ellis, group leader of the Centre for Synthetic Biology at Imperial College London, said:
These could do tasks like sensing and recording, or even in-situ synthesis of therapeutic molecules as and when they are needed.
Images from MIT, Cell Systems, and Shutterstock.